As the Chief Medical Officer, Professor Dame Sally Davies, highlights today “danger posed by growing resistance to antibiotics should be ranked along with terrorism on a list of threats to the nation”. Professor Dame Sally Davies said diseases are evolving faster than the drugs that exist to treat them and antibiotic resistance is “a ticking time bomb“.
This is a subject of great interest to scientists in ICaMB, particularly the Centre for Bacterial Cell Biology, which brings together a world-class group of scientists researching bacterial physiology and the host response to bacterial infections. A major focus of this research involves:
- Exploring alternative targets for antibiotic development
- Understanding how antibiotics attack bacterial cells
- Investigating how bacteria overcome such an attack
Tonight (March 11th 2013), work from the group of Kenn Gerdes and Etienne Maisonneuve, a post-doc in his group, will be featured on the BBC programme “Bang Goes the Theory” in an episode about Antibiotics.
Kenn and Etienne’s research focuses on persister cells, bacterial cells that can tolerate and survive attack by antibiotics. Importantly, ALL bacteria analysed so far generate “persister cells” and understanding this is key to understanding how bacteria avoid antibiotic attack. “Bang Goes the Theory” will show a movie showing how these persister cells are identified in a bacterial population.
Penicillin inhibits synthesis of the bacterial cell wall, causing the cell to explode (or ‘lyse’) due to the high pressure inside the cell. This is why penicillin and similar drugs are very effective in curing infections caused by penicillin-sensitive bacteria. In the movie, see how the cells suddenly explode when penicillin is added but notice how one cell, the persister cells (darker cells not exploding on the left panel) are surviving.
These persister cells evade killing by antibiotics because they grow extremely slowly. Persisters are proposed to be one explanation for infection relapses or chronic infections so Kenn and Ethienne’s work is extremely important for understanding how we should use antibiotics.
To do this work, Etienne used state-of-the-art technology – microfluidics – to follow the growth of individual bacterial cells under a microscope. These devices are smaller than a penny coin and the chambers where the bacteria are grown can be less than 1 mm across. This technique allows us to grow bacteria in one condition but, at a flip of a switch, change it and watch the response, as seen in the movie.
CBCB academics have used the ability to explode Escherichia coli to explore the what, when and how of antibiotics with Year 9 school students as part of the University engagement program Leading Edge.
With these students, we have developed a protocol to allow them to observe E. coli in the act of exploding after adding penicillin.
Persistence is not Resistance: It is important to understand the difference between these two terms. Antibiotic resistant and sensitive bacteria are able to generate persister cells, that are not effected by antibiotic attack. Antibiotic Resistance is a trait acquired by the whole population.
The Scientific Specifics: Over the last few years, several scientific breakthroughs made by the Gerdes group have, for the first time, given insight into how bacteria control the switch to slow growth and persistence. Persister cells can survive penicillin because the bacteria hibernate for a period, during which they don’t synthesize their cell wall. They can then “wake up” when the antibiotic treatment is over, causing a new infection. In young and healthy people this is usually not a problem, because the rare non-growing bacteria are removed by the immune system. However, elderly individuals or those with a weakened immune system, it is often not efficient enough to permit clearance of the rare bacteria that survive the treatment, allowing the infection to “break out”.
The Gerdes group has shown that a certain class of gene that inhibits cell growth are turned on in one cell per 10,000. These discoveries open avenues to generate novel antibiotics and treatment regimes in the future. However, before that, their group is investigating if similar mechanisms allow pathogenic bacteria, such as Mycobacterium tuberculosis, to evade killing by antibiotics.